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- W4361946019 abstract "<div>Abstract<p><b>Purpose:</b> Adoptive transfer of Epstein–Barr virus (EBV)–specific and cytomegalovirus (CMV)-specific cytotoxic T cells (CTL) genetically modified to express a chimeric antigen receptor (CAR) induces objective tumor responses in clinical trials. <i>In vivo</i> expansion and persistence of these cells are crucial to achieve sustained clinical responses. We aimed to develop an off-the-shelf whole-cell vaccine to boost CAR-redirected virus-specific CTLs <i>in vivo</i> after adoptive transfer. As proof of principle, we validated our vaccine approach by boosting CMV-specific CTLs (CMV-CTLs) engineered with a CAR that targets the GD2 antigen.</p><p><b>Experimental Design:</b> We generated the whole-cell vaccine by engineering the K562 cell line to express the CMV-pp65 protein and the immune stimulatory molecules CD40L and OX40L. Single-cell–derived clones were used to stimulate CMV-CTLs <i>in vitro</i> and <i>in vivo</i> in a xenograft model. We also assessed whether the <i>in vivo</i> boosting of CAR-redirected CMV-CTLs with the whole-cell vaccine enhances the antitumor responses. Finally, we addressed potential safety concerns by including the inducible safety switch caspase9 (<i>iC9</i>) gene in the whole-cell vaccine.</p><p><b>Results:</b> We found that K562-expressing CMV-pp65, CD40L, and OX40L effectively stimulate CMV-specific responses <i>in vitro</i> by promoting antigen cross-presentation to professional antigen-presenting cells (APCs). Vaccination also enhances antitumor effects of CAR-redirected CMV-CTLs in xenograft tumor models. Activation of the <i>iC9</i> gene successfully induces growth arrest of engineered K562 implanted in mice.</p><p><b>Conclusions:</b> Vaccination with a whole-cell vaccine obtained from K562 engineered to express CMV-pp65, CD40L, OX40L and <i>iC9</i> can safely enhance the antitumor effects of CAR-redirected CMV-CTLs. <i>Clin Cancer Res; 21(13); 2952–62. ©2015 AACR</i>.</p></div>" @default.
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- W4361946019 date "2023-03-31" @default.
- W4361946019 modified "2023-10-14" @default.
- W4361946019 title "Data from K562-Derived Whole-Cell Vaccine Enhances Antitumor Responses of CAR-Redirected Virus-Specific Cytotoxic T Lymphocytes <i>In Vivo</i>" @default.
- W4361946019 doi "https://doi.org/10.1158/1078-0432.c.6523740" @default.
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